Blurring of High-Resolution Data Shows that the Effect of Intrinsic Nucleosome Occupancy on Transcription Factor Binding is Mostly Regional, Not Local 英文参考文献.docVIP

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Blurring of High-Resolution Data Shows that the Effect of Intrinsic Nucleosome Occupancy on Transcription Factor Binding is Mostly Regional, Not Local 英文参考文献.doc

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Blurring of High-Resolution Data Shows that the Effect of Intrinsic Nucleosome Occupancy on Transcription Factor Binding is Mostly Regional, Not Local 英文参考文献

BlurringofHigh-ResolutionDataShowsthattheEffectof IntrinsicNucleosomeOccupancyonTranscriptionFactor BindingisMostlyRegional,NotLocal WeeSiongGoh,YuriyOrlov,JingmeiLi,NeilD.Clarke* ComputationalandSystemsBiology,GenomeInstituteofSingapore,Singapore Abstract Genome wide maps of nucleosome occupancy in yeast have recently been produced through deep sequencing of nuclease-protectedDNA.Thesemapshavebeenobtainedfrombothcrosslinkedanduncrosslinkedchromatininvivo,and fromchromatinassembledfromgenomicDNAandnucleosomesinvitro.Here,weanalyzethesemapsincombinationwith existing ChIP-chip data, and with new ChIP-qPCR experiments reported here. We show that the apparent nucleosome density in crosslinked chromatin, when compared to uncrosslinked chromatin, is preferentially increased at transcription factor(TF)bindingsites,suggestingastrategyformappinggenerictranscriptionfactorbindingsitesthatwouldnotrequire immunoprecipitation ofaparticularfactor. Wealso confirmprevious conclusions thattheintrinsic,sequencedependent bindingofnucleosomeshelpsdeterminethelocalizationofTFbindingsites.However,wefindthattheassociationbetween lownucleosome occupancy andTFbindingis typically greaterifoccupancy atasite isaveragedover a600bpwindow, rather than using the occupancy at the binding site itself. We have also incorporated intrinsic nucleosome binding occupanciesasweightsinacomputationalmodelforTFbinding,andbythismeasureaswellwefindbetterpredictionif the high resolution nucleosome occupancy data is averaged over 600bp. We suggest that the intrinsic DNA binding specificity of nucleosomes plays a role in TF binding site selection not so much through the specification of precise nucleosomepositionsthatpermitoroccludebinding,butratherthroughthecreationoflowoccupancyregionsthatcan accommodatecompetitionfromTFsthroughrearrangementofnucleosomes. Citation:GohWS,OrlovY,LiJ,ClarkeND(2010)BlurringofHigh-ResolutionDataShowsthattheEffectofIntrinsicNucleosomeOccupancyonTranscription FactorBindingisMostly